ACTIVATED ALFA-2 MACROGLOBULIN (alpha2M*) MEDIATES INTRACELLULAR SIGNALING PATHWAYS VIA THE ENDOCYTIC RECEPTOR LRP-1

CÁCERES L, BONACCI G, CESCHIN D, CHIABRANDO G.

Iguazo, Misiones

Congreso; XL Annual Meeting ARGENTINE SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY; 2004

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Alpha-2-macroglobulin (alpha2M) is the most important human proteinase inhibitor, upon binding to proteinases undergoes a conformational change, activated alpha2M (alpha2M*), that expose recognition receptor site allowed its interaction with LRP-1 receptor. LRP-1 is a member of the LDL receptor gene family that binds to a variety of ligands, some of which trigger signaling transduction. Previously we have demonstrated that alpha2M* has proliferative effects and increase intracellular calcium in J774 macrophage derived cell line LRP positive. In this work we evaluate the alpha2M* effect down-stream to LRP-1 interaction measuring MAPK phosphorylation in J774 cell cultured in the presence and absence of LPS (a down regulator factor of LRP-1). By Western blotting we observe that alpha2M* 20 nM and 70 nM promote ERK-1/2 phosphorylation at different times (15, 30, and 60 min.). On the other hand, when J774 were treated with LPS 30 microgr/ml for 24 hs we demonstrate that intracellular signaling pathways were not activated in the presence of alpha2M*. In addition, we analyse the alpha2M* effect on ERK-1/2 phosphorylation in HT-1080 fibroblast derived cell LRP-1 positive. Like J774, alpha2M* 20 nM and 70 nM promotes ERK-1/2 phosphorylation. In conclusion, in this work we demonstrate that alpha2M* can activate intracellular signalling pathways mediated by LRP-1.